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Cited by 2,229interferon and immune responsesSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

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Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K. D. +740 more·2020·Science
DOI 10.1126/science.abd4570PMC PMC7857407
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Abstract

The genetics underlying severe COVID-19: The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 ; see also p. 404

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  • People who cannot produce or respond to type I interferon face a higher risk of severe COVID-19.

    “Furthermore, humans deficient in producing or responding to type I interferon have an increased risk of severe COVID-19 (refs66–68).”

    From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [66]

  • Individuals with defective type I IFN responses have very high risk of severe or fatal COVID-19.

    “The risk of a poor early innate immune response to SARS-CoV-2 is highlighted by the striking findings of very high risk of severe or fatal COVID-19 in individuals with defective type I IFN responses (Bastard et al., 2020; Zhang et al., 2020).”

    From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Zhang et al., 2020

  • Severe COVID-19 patients can carry loss-of-function variants in multiple genes linked to TLR3 and IRF7 pathways, which are involved in inducing and amplifying type I interferons.

    “severe patients can also carry loss of function variants in multiple genes linked to TLR3 and IRF7 pathways, involved in both the induction and amplification of type I IFNs105.”

    From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [105]

  • Discoveries of inborn errors of type I interferon immunity and autoantibodies against type I interferons in the most severe cases of Covid-19 suggest that an inadequate antiviral response may be contributory in some patients.

    “Alternatively, the discoveries of inborn errors of type I interferon immunity and autoantibodies against type I interferons in the most severe cases of Covid-19 suggest that an inadequate antiviral response may be contributory in some patients with Covid-19.94,95”

    From Cytokine storm (2020) · cites this paper as [94]

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Research works printed but not linked: 2

  1. [1]Morens DM, Fauci AS, Emerging Pandemic Diseases: How We Got To COVID-19. Cell, (2020). PMC7598893 33125895
  2. [40]Robbiani DF,, Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437– 442 (2020). 32555388 PMC7442695

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Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., Ogishi, M., Sabli, I. K. D., Hodeib, S., Korol, C., Rosain, J., Bilguvar, K., Ye, J., Bolze, A., Bigio, B., Yang, R., Arias, A. A., Zhou, Q., Zhang, Y., Onodi, F., Korniotis, S., Karpf, L., Philippot, Q., Chbihi, M., Bonnet-Madin, L., Dorgham, K., Smith, N., Schneider, W. M., Razooky, B. S., Hoffmann, H.-H., Michailidis, E., Moens, L., Han, J. E., Lorenzo, L., Bizien, L., Meade, P., Neehus, A.-L., Ugurbil, A. C., Corneau, A., Kerner, G., Zhang, P., Rapaport, F., Seeleuthner, Y., Manry, J., Masson, C., Schmitt, Y., Schlüter, A., Le Voyer, T., Khan, T., Li, J., Fellay, J., Roussel, L., Shahrooei, M., Alosaimi, M. F., Mansouri, D., Al-Saud, H., Al-Mulla, F., Almourfi, F., Al-Muhsen, S. Z., Alsohime, F., Al Turki, S., Hasanato, R., van de Beek, D., Biondi, A., Bettini, L. R., D’Angio’, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A. J., Tompkins, M. F., Alba, C., Vandernoot, I., Goffard, J.-C., Smits, G., Migeotte, I., Haerynck, F., Soler-Palacin, P., Martin-Nalda, A., Colobran, R., Morange, P.-E., Keles, S., Çölkesen, F., Ozcelik, T., Yasar, K. K., Senoglu, S., Karabela, Ş. N., Rodríguez-Gallego, C., Novelli, G., Hraiech, S., Tandjaoui-Lambiotte, Y., Duval, X., Laouénan, C., Clinicians, C.-S., Clinicians, C., Imagine COVID Group, French COVID Cohort Study Group, Cohort, C.-C., Biobank, A. U. C.-1., Effort, C. H. G., NIAID-USUHS/TAGC COVID Immunity Group, Snow, A. L., Dalgard, C. L., Milner, J. D., Vinh, D. C., Mogensen, T. H., Marr, N., Spaan, A. N., Boisson, B., Boisson-Dupuis, S., Bustamante, J., Puel, A., Ciancanelli, M. J., Meyts, I., Maniatis, T., Soumelis, V., Amara, A., Nussenzweig, M., García-Sastre, A., Krammer, F., Pujol, A., Duffy, D., Lifton, R. P., Zhang, S.-Y., Gorochov, G., Béziat, V., Jouanguy, E., Sancho-Shimizu, V., Rice, C. M., Abel, L., Notarangelo, L. D., Cobat, A., Su, H. 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Affiliations
  • Rockefeller University (US)
  • Hôpital Necker-Enfants Malades (FR)
  • Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Imperial College London (GB)
  • Yale Center for Genome Analysis and Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
  • Columbia University (US)
  • National Institutes of Health (US)
  • Inserm (FR)
  • Laboratory of Genomes & Cell Biology of Disease, INSERM U944, CNRS UMR 7212, Université de Paris, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France.
  • Institut Pasteur (FR)
  • Universitair Ziekenhuis Leuven (BE)
  • Icahn School of Medicine at Mount Sinai (US)
  • Sorbonne Université (FR)
  • Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Bioinformatics Platform, Structure Fédérative de Recherche Necker, INSERM UMR1163, Université de Paris, Imagine Institute, Paris, France.
  • Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, CIBERER U759, and Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
  • Sidra Medical and Research Center (QA)
  • McGill University Health Centre (CA)
  • King Saud University (SA)
  • National Center of Genomics Technology, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
  • King Abdulaziz City for Science and Technology (SA)
  • King Saud Medical City (SA)
  • Translational Pathology, Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Misery of National Guard Health Affairs, Riyadh, Saudi Arabia.
  • Azienda Ospedaliera San Gerardo (IT)
  • Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy.
  • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
  • Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali di Brescia, Brescia, Italy.
  • Uniformed Services University of the Health Sciences (US)
  • Université Libre de Bruxelles (BE)
  • Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.
  • Aix Marseille Univ, INSERM, INRAE, C2VN, CHU Timone, Marseille, France.
  • Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR)
  • Aarhus University (DK)
  • Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Division of Pediatric Allergy, Immunology and Rheumatology, Columbia University, New York, USA.
  • Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
  • Centre National de la Recherche Scientifique (FR)
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Yale University (US)
  • University of Rome Tor Vergata (IT)
  • Konya Eğitim ve Araştırma Hastanesi (TR)
  • Universitat Autònoma de Barcelona (ES)
  • Helix (United States) (US)
  • Universidad Fernando Pessoa Canarias (ES)
  • Necmettin Erbakan University (TR)
  • Masih Daneshvari Hospital (IR)
  • Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (FR)
  • CIC Rennes (FR)
  • New York Genome Center (US)
  • Amsterdam Neuroscience (NL)
  • Dasman Diabetes Institute (KW)
  • Ghent University Hospital (BE)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • KU Leuven (BE)
Corresponding author
  • Bastard, Paul
  • Liu, Zhiyong
  • Chen, Jie
  • Ogishi, Masato
  • Sabli, Ira K. D.
  • Hodeib, Stephanie
  • Korol, Cecilia
  • Rosain, Jérémie
  • Ye, Junqiang
  • Bigio, Benedetta
  • Yang, Rui
  • Zhou, Qinhua
  • Zhang, Yu
  • Lifton, Richard P.
  • Zhang, Shen-Ying
  • Gorochov, Guy
  • Béziat, Vivien
  • Jouanguy, Emmanuelle
  • Rice, Charles M.
  • Cobat, Aurélie
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-10-23
Volume
370
Issue
6515
Pages
eabd4570
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.abd4570
PMC
PMC7857407
OpenAlex
W3087862874
Cited by
2,229
References
40
Citations by year
2026: 85 · 2025: 114 · 2024: 220 · 2023: 322 · 2022: 521 · 2021: 819 · 2020: 147
FWCI
158.59
Type
journal article
Language
en
Open access
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  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Figshare (submittedVersion, cc-by)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
  • Use Siena air (University of Siena) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (R01AI088364)
  • Howard Hughes Medical Institute
  • ST. GILES FOUNDATION
  • National Center for Advancing Translational Sciences
  • Rockefeller University
  • French National Research Agency (ANR-10-IAHU-01)
  • the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID)
  • National Human Genome Research Institute (UM1HG006504 and U24HG008956)
  • the French Foundation for Medical Research (EQU201903007798)
  • NIH Clinical and Translational Science Award (UL1 TR001866)
  • Emergent Ventures (fast grant)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
severe COVID-19, interferon lambda, interferon omega, interferon alpha 2, genetic susceptibility, candidate gene mutations, COVID-19 pneumonia, autoimmunity
MeSH terms
Betacoronavirus, Loss of Function Mutation, COVID-19, SARS-CoV-2, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Child, Child, Preschool, Female, Humans, Infant, Interferon Type I, Male, Middle Aged, Pneumonia, Viral, Coronavirus Infections, Genetic Predisposition to Disease, Interferon Regulatory Factor-7, Toll-Like Receptor 3, Receptor, Interferon alpha-beta, Young Adult, Genetic Loci, Asymptomatic Infections, Pandemics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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